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An animal model mimicking pedunculopontine nucleus cholinergic degeneration in Parkinson's disease

Lookup NU author(s): Dr Ilse Pienaar, Dr Joanna Elson, Alex Bury

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Abstract

A rostral brainstem structure, the pedunculopontine nucleus (PPN), is severely affected by Parkinson's disease (PD) pathology and is regarded a promising target for therapeutic deep-brain stimulation (DBS). However, understanding the PPN's role in PD and assessing the potential of DBS are hampered by the lack of a suitable model of PPN degeneration. Rats were rendered Parkinsonian through a unilateral substantia nigra pars compacta (SNpc) stereotaxic injection of the proteasome inhibitor Lactacystin, to investigate whether the lesion's pathological effects spread to impact the integrity of PPN cholinergic neurons which are affected in PD. At 5 weeks post-surgery, stereological analysis revealed that the lesion caused a 48 % loss of dopaminergic SNpc neurons and a 61 % loss of PPN cholinergic neurons, accompanied by substantial somatic hypotrophy in the remaining cholinergic neurons. Magnetic resonance imaging revealed T2 signal hyper-/hypointensity in the PPN of the injected hemisphere, respectively at weeks 3 and 5 post-lesion. Moreover, isolated PPN cholinergic neurons revealed no significant alterations in key autophagy mRNA levels, suggesting that autophagy-related mechanisms fail to protect the PPN against Lactacystin-induced cellular changes. Hence, the current results suggest that the Lactacystin PD model offers a suitable model for investigating the role of the PPN in PD.

Publication metadata

Author(s): Pienaar IS, Harrison IF, Elson JL, Bury A, Woll P, Simon AK, Dexter DT

Publication type: Article

Publication status: Published

Journal: Brain Structure and Function

Year: 2015

Volume: 220

Issue: 1

Pages: 479-500

Print publication date: 01/01/2015

Online publication date: 29/11/2013

Acceptance date: 29/10/2013

ISSN (print): 1863-2653

ISSN (electronic): 1863-2661

Publisher: Springer

URL: http://dx.doi.org/10.1007/s00429-013-0669-5

DOI: 10.1007/s00429-013-0669-5

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